The selective role of membrane IgG in the antigen-induced inhibition of human in vitro antibody synthesis.
IgG-anti-tetanus toxoid-producing B cell precursors from recently immunized individuals can be stimulated by pokeweed mitogen and T cells to produce IgG-Tet antibodies in vitro. Treatment of these cells with tetanus toxoid selectively inhibits the synthesis of IgG-Tet. Because the IgG-Tet precursors display heterogeneity in their surface isotypes (mu, delta, gamma), the aim of this study was to determine the surface isotype responsible for transmitting this antigen-induced inhibitory signal to the B cell. B cells were fractionated by rosetting techniques on the basis of surface IgM or IgD. The 4 resulting B cell subsets (SIgM+, sIgM-, sIgD+, sIgD-) were found to be equally susceptible to antigen-induced inhibition. Experiments were then performed with anti-isotype antibodies to investigate further the roles of sIgM, sIgD, and sIgG in antigen inhibition. Treatment of peripheral blood lymphocytes with 10 micrograms/ml of anti-gamma antibody inhibited IgG-Tet antibody production, whereas the addition of up to 100 micrograms of anti-mu or anti-delta antibodies did not. Tetanus toxoid and anti-gamma antibody inhibition of IgG-Tet synthesis in vitro followed similar temporal kinetics, with the IgG-Tet precursors being sensitive to inhibition by either tetanus toxoid or anti-gamma antibodies during the first 3 days of culture and not becoming totally resistant to these agents until day 5 of culture. Capping off of sIgG receptors, with the subsequent addition of tetanus toxoid, abolished the antigen-induced inhibition of IgG-Tet seen previously, whereas capping off of sIgD or sIgM did not affect antigen inhibition of IgG-Tet antibodies. These results implicate sIgG molecules as those responsible for rendering IgG-Tet precursors susceptible to antigen-induced inhibition.
D000818:Animals; D000917:Antibody Formation; D000941:Antigens; D001402:B-Lymphocytes / Q000276:immunology; D002469:Cell Separation; D006801:Humans; D007072:Immunoglobulin D / Q000276:immunology; D007074:Immunoglobulin G; D007075:Immunoglobulin M / Q000276:immunology; D007138:Immunoglobulin delta-Chains / Q000276:immunology; D007142:Immunoglobulin gamma-Chains / Q000276:immunology; D007148:Immunoglobulin mu-Chains / Q000276:immunology; D011817:Rabbits; D011947:Receptors, Antigen, B-Cell; D013745:Tetanus Toxoid / Q000276:immunology; D013997:Time Factors
D000941:Antigens; D007072:Immunoglobulin D; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007138:Immunoglobulin delta-Chains; D007142:Immunoglobulin gamma-Chains; D007148:Immunoglobulin mu-Chains; D011947:Receptors, Antigen, B-Cell; D013745:Tetanus Toxoid